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Behçet's disease (Adamantiades-Behçet's disease).

Kaneko F, Togashi A, Saito S, Sakuma H, Oyama N, Nakamura K, Yokota K, Oguma K - Clin. Dev. Immunol. (2010)

Bottom Line: Adamantiades-Behçet's disease (ABD) is characterized by starting with oral aphthous ulceration and developing of the systemic involvements.Although Hsp-65/60 has homologies with the respective T cell epitope, it stimulates peripheral blood mononuclear cells (PBMCs) from ABD patients.On the other hand, some peptides of Hsp-65 were found to reduce IL-8 and IL-12 production from PBMCs of ABD patients in active stage.

View Article: PubMed Central - PubMed

Affiliation: Institute of Dermato-Immunology and Allergy, Southern TOHOKU Research Institute for Neuroscience, 7-115 Yatsuyamada, Koriyama, Fukushima 963-8563, Japan. f.kaneko@mt.strins.or.jp

ABSTRACT
Adamantiades-Behçet's disease (ABD) is characterized by starting with oral aphthous ulceration and developing of the systemic involvements. The pathogenesis of ABD is closely correlated with the genetic factors and the triggering factors which acquire delayed-type hypersensitivity reaction against oral streptococci mediated by IL-12 cytokine family. HLA-B51 is associated in more than 60% of the patients and its restricted CD8+ T cell response is clearly correlated with the target tissues. Bes-1 gene encoded partial S. sanguinis genome which is highly homologous with retinal protein, and 65 kD heat shock protein (Hsp-65) released from streptococci is playing an important role with human Hsp-60 in the pathogenesis of ABD. Although Hsp-65/60 has homologies with the respective T cell epitope, it stimulates peripheral blood mononuclear cells (PBMCs) from ABD patients. On the other hand, some peptides of Hsp-65 were found to reduce IL-8 and IL-12 production from PBMCs of ABD patients in active stage.

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Related in: MedlinePlus

IL-8 production from MONO cells activated by S. sanguinis antigen was suppressed by LO1 and UK in a dose-dependent manner.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2967828&req=5

fig3: IL-8 production from MONO cells activated by S. sanguinis antigen was suppressed by LO1 and UK in a dose-dependent manner.

Mentions: Then, we analyzed Hsp-65 derived from S. sanguinis to find the homologous peptides to T cell epitope of ABD patients and also to find how the peptides reduce the production of cytokines from PBMCs of ABD patients in active disease stage. The 4 peptides of Hsp-65 were shown to significantly stimulate and undergo CD4+ and CD8+ T cell apoptosis in PBMCs from ABD patients. Hsp-60 also seemed to stimulate them similarly, because the peptide of Hsp-60 (336–351) was identified to be highly homologous to T cell epitope [14, 35–39]. The peptides LO1 (249–264), IIIa (365–384), IIIb (395–413), LO2 (480–499), LO3 (504–518), and UK (311–326) corresponding to the human Hsp60 (336–351) (Table 1) were applied for activated T cells of ABD patients in vitro to lead immunotoleration. PBMCs from 7 active ABD patients and 5 HIs were incubated with and without these peptides and 7 days after incubation mainly IL-8 and IL-12 were measured and compared with those from PBMCs of active ABD patients incubated without the peptides as controls. Although IL-12 and IL-8 were naturally produced from PBMCs of active ABD patients, the significant reduction of inflammatory cytokines was found by the 5 peptides, LO1, LO2, LO3, IIIb, and UK. To understand the suppressive mechanisms of the cytokine production in PBMCs from active ABD patients, we tried to find the binding sites of the peptides on monocytes by cDNA chips (Gene Chip; Human Genome) using NOMO-1 cells (human macrophage cell line) which were activated by S. sanguinis antigen. The NOMO-1 cells incubated with LO1 were suppressed to produce IL-8 (Figure 3). CD58 molecule and/or FK506-binding protein were highly expressed on the cell surface of the NOMO-1 cells by LO1 [27, 32]. It is considered that activated T cells of ABD patients might be led to apopthosis by binding of LO1 on the receptors of the cells.


Behçet's disease (Adamantiades-Behçet's disease).

Kaneko F, Togashi A, Saito S, Sakuma H, Oyama N, Nakamura K, Yokota K, Oguma K - Clin. Dev. Immunol. (2010)

IL-8 production from MONO cells activated by S. sanguinis antigen was suppressed by LO1 and UK in a dose-dependent manner.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2967828&req=5

fig3: IL-8 production from MONO cells activated by S. sanguinis antigen was suppressed by LO1 and UK in a dose-dependent manner.
Mentions: Then, we analyzed Hsp-65 derived from S. sanguinis to find the homologous peptides to T cell epitope of ABD patients and also to find how the peptides reduce the production of cytokines from PBMCs of ABD patients in active disease stage. The 4 peptides of Hsp-65 were shown to significantly stimulate and undergo CD4+ and CD8+ T cell apoptosis in PBMCs from ABD patients. Hsp-60 also seemed to stimulate them similarly, because the peptide of Hsp-60 (336–351) was identified to be highly homologous to T cell epitope [14, 35–39]. The peptides LO1 (249–264), IIIa (365–384), IIIb (395–413), LO2 (480–499), LO3 (504–518), and UK (311–326) corresponding to the human Hsp60 (336–351) (Table 1) were applied for activated T cells of ABD patients in vitro to lead immunotoleration. PBMCs from 7 active ABD patients and 5 HIs were incubated with and without these peptides and 7 days after incubation mainly IL-8 and IL-12 were measured and compared with those from PBMCs of active ABD patients incubated without the peptides as controls. Although IL-12 and IL-8 were naturally produced from PBMCs of active ABD patients, the significant reduction of inflammatory cytokines was found by the 5 peptides, LO1, LO2, LO3, IIIb, and UK. To understand the suppressive mechanisms of the cytokine production in PBMCs from active ABD patients, we tried to find the binding sites of the peptides on monocytes by cDNA chips (Gene Chip; Human Genome) using NOMO-1 cells (human macrophage cell line) which were activated by S. sanguinis antigen. The NOMO-1 cells incubated with LO1 were suppressed to produce IL-8 (Figure 3). CD58 molecule and/or FK506-binding protein were highly expressed on the cell surface of the NOMO-1 cells by LO1 [27, 32]. It is considered that activated T cells of ABD patients might be led to apopthosis by binding of LO1 on the receptors of the cells.

Bottom Line: Adamantiades-Behçet's disease (ABD) is characterized by starting with oral aphthous ulceration and developing of the systemic involvements.Although Hsp-65/60 has homologies with the respective T cell epitope, it stimulates peripheral blood mononuclear cells (PBMCs) from ABD patients.On the other hand, some peptides of Hsp-65 were found to reduce IL-8 and IL-12 production from PBMCs of ABD patients in active stage.

View Article: PubMed Central - PubMed

Affiliation: Institute of Dermato-Immunology and Allergy, Southern TOHOKU Research Institute for Neuroscience, 7-115 Yatsuyamada, Koriyama, Fukushima 963-8563, Japan. f.kaneko@mt.strins.or.jp

ABSTRACT
Adamantiades-Behçet's disease (ABD) is characterized by starting with oral aphthous ulceration and developing of the systemic involvements. The pathogenesis of ABD is closely correlated with the genetic factors and the triggering factors which acquire delayed-type hypersensitivity reaction against oral streptococci mediated by IL-12 cytokine family. HLA-B51 is associated in more than 60% of the patients and its restricted CD8+ T cell response is clearly correlated with the target tissues. Bes-1 gene encoded partial S. sanguinis genome which is highly homologous with retinal protein, and 65 kD heat shock protein (Hsp-65) released from streptococci is playing an important role with human Hsp-60 in the pathogenesis of ABD. Although Hsp-65/60 has homologies with the respective T cell epitope, it stimulates peripheral blood mononuclear cells (PBMCs) from ABD patients. On the other hand, some peptides of Hsp-65 were found to reduce IL-8 and IL-12 production from PBMCs of ABD patients in active stage.

Show MeSH
Related in: MedlinePlus